Immunotherapy during the acute SHIV infection of macaques confers long-term suppression of viremia

Author:

Nishimura Yoshiaki1ORCID,Donau Olivia K.1ORCID,Dias Joana2ORCID,Ferrando-Martinez Sara2ORCID,Jesteadt Eric1ORCID,Sadjadpour Reza1ORCID,Gautam Rajeev1ORCID,Buckler-White Alicia1ORCID,Geleziunas Romas3ORCID,Koup Richard A.2ORCID,Nussenzweig Michel C.45ORCID,Martin Malcolm A.1ORCID

Affiliation:

1. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

2. Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

3. Gilead Sciences, Inc., Foster City, CA

4. Laboratory of Molecular Immunology, Rockefeller University, New York, NY

5. Howard Hughes Medical Institute, Rockefeller University, New York, NY

Abstract

We report that combination bNAb immunotherapy initiated on day 3 post-infection (PI) maintained durable CD8+ T cell–mediated suppression of SHIVAD8 viremia and preinoculation levels of CD4+ T cells in 9 of 13 treated monkeys during nearly 6 yr of observation, as assessed by successive CD8+ T cell–depletion experiments. In an extension of that study, two treatment interventions (bNAbs alone or cART plus bNAbs) beginning on week 2 PI were conducted and conferred controller status to 7 of 12 monkeys that was also dependent on control mediated by CD8+ cells. However, the median time to suppression of plasma viremia following intervention on week 2 was markedly delayed (85 wk) compared with combination bNAb immunotherapy initiated on day 3 (39 wk). In both cases, the principal correlate of virus control was the induction of CD8+ T cellular immunity.

Funder

Intramural Research Program of the National Institute of Allergy and Infectious Diseases

Bill and Melinda Gates Foundation

National Institute of Allergy and Infectious Diseases

National Institutes of Health Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery

Rockefeller University

Robertson Foundation

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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